Abstract

The major component of senile plaques and vascular amyloid in Alzheimer's disease (AD) brains is the amyloid β protein (Aβ). Besides Aβ, several other proteins have been identified in these lesions, in particular heparan sulfate proteoglycans (HSPG). However, it is still unclear, what causes the excessive accumulation of HSPG in AD brains. Therefore, we investigated if Aβ may influence production and expression of two major Aβ-associated HSPG species, agrin and glypican-1. When human brain pericytes (HBP) were cultured in the presence of Aβ, protein and mRNA expression of both agrin and glypican-1 were increased and more radioactive sulfate was incorporated in the glycosaminoglycan fraction of Aβ-treated HBP. Furthermore, after Aβ treatment, these HSPG were found in association with the amyloid fibrils attached to the cell membrane, in contrast to the intracellular agrin and glypican-1 staining observed in untreated cells. We conclude that Aβ can modulate the cellular expression of agrin and glypican-1, which may contribute to the accumulation of these HSPG in AD lesions.

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